AB0377 CHARACTERISTICS OF BLOOD TEST RESULTS IN D2T RA BEFORE INITIATING DMARDS TREATMENT: HIGHER IFN AND LESS IL-6 INVOLVEMENT WERE PRESUMED BY PROPENSITY SCORE MATCHING ANALYSIS
Authors: Y. Nishiura, Y. Nakai, M. Tokunaga, Y. Koyama
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Difficult-to-treat rheumatoid arthritis (D2T RA) is a new concept of RA patients who do not achieve remission despite several types of treatment. It remains to be elucidated what makes the clinical differences between D2T RA and non-D2T RA. <h3>Objectives</h3> To analyze blood test results of D2T RA patients and non-D2T RA patients before initiating treatment to see if there are differences in their trends and characteristics. <h3>Methods</h3> We conducted a retrospective, observational cohort study using blood tests, including patients diagnosed with RA who attended our institute. The patients were divided into two groups; those who satisfied EULAR definition of D2T were included as D2T-RA, and the others who did not meet the definition after at least 2 years of treatment were included as non-D2T RA patients. To eliminate the influence of treatment on blood test data and disease activity, only patients whose blood test data existed prior to starting treatment with disease modifying antirheumatic drugs (DMARDs) were picked from both groups. The two groups were then matched 1:1 using propensity scores adjusted for gender, age, duration of RA disease, BMI, smoking habits, and DAS28-ESR. Comparisons were made between these two adjusted groups for each blood test item using an independent-samples t-test. SPSS statistical software was used. <h3>Results</h3> Ninety-four RA patients (mean age 60.3±12.6 years, 74% female) were included, 23 (mean age 55.4±13.2 years, 83% female) belonged to D2T RA and 71 (mean age 61.8±12.1 years, 72% female) to non-D2T RA. Of these, 13 cases of D2T RA and 2 cases of non-D2T RA were excluded due to lack of blood test data before starting DMARDs therapy. D2T RA patients were 57.6 ± 11.1 years old (86% female) and non-D2T RA patients were 57.0 ± 10.1 years old (100% female). In D2T RA, mean corpuscular volume (MCV: D2T vs non-D2T = 95.6±3.8 vs 85.6±3.9, p&lt;0.001), mean corpuscular hemoglobin (MCH: 32.0±1.7 vs 28.7±1.7, p=0.003), serum transferrin saturation (TSAT) ratio (Fe*100/TIBC: 32.3±7.2 vs 19.3±9.6, p=0.020) and lactate dehydrogenase (LDH: 203±33U/L vs 164±16U/L, p=0.026) were significantly higher. On the other hand, unbound iron binding capacity (UIBC: 184±42 vs 253±35, p=0.007) was significantly lower in D2T RA. Although it was not reaching statistical significance, lower lymphocyte count (1068±304/μ vs 1816±867/μ, p=0.052), fewer red blood cell (RBC: 4.03±0.34*10<sup>6</sup>/μ vs 4.45±0.51*10<sup>6/</sup>μL, p=0.096) and higher neutrophil ratio (76.9±8.2% vs 66.5±10.7%, p=0.065) were observed in D2T RA. <h3>Conclusion</h3> In a comparison of blood test results before initiating treatment, the differences between D2T and non-D2T cases were mainly related to iron metabolism and white blood cell differential. Patients with non-D2T RA had significantly lower TSAT than patients with D2T RA, with a trend toward having a microcytic hypochromic anemia. This reminds us of the involvement of hepcidin and may suggest that Interleukin 6 (IL-6) is involved in the pathogenesis of non-D2T RA but it is less involved in that of D2T RA 1). The hypothesis explains the clinical features of resistance to treatment with IL-6 inhibitors in patients with D2T-RA. Furthermore, a clear lymphocyte count decrease was observed in D2T RA cases, suggesting a strong IFN signature 2). Interestingly, D2T RA cases showed a greater tendency toward anemia than non-D2T RA cases, with a tendency toward macrocytic rather than microcytic anemia. A trend of increased neutrophil ratio was also observed in D2T RA cases. On the other hand, there were no significant differences in immunological background, such as rheumatoid factor (RF) nor anti-citrullinated protein antibodies (ACPA). <h3>References</h3> [1]Y. Chen <i>et al.</i>, Serum Levels of Hepcidin in Rheumatoid Arthritis and Its Correlation with Disease Activity and Anemia: A Meta-analysis. <i>Immunol Invest</i> 50, 243-258 (2021). [2]T. Iwasaki <i>et al.</i>, Dynamics of Type I and Type II Interferon Signature Determines Responsiveness to Anti-TNF Therapy in Rheumatoid Arthritis. <i>Frontiers in immunology</i> 13, 901437 (2022). <h3>Acknowledgements</h3> We gratefully acknowledge the diligent work of Y. Koumori. <h3>Disclosure of Interests</h3> Yoshinori Nishiura: None declared, Yu Nakai: None declared, Moe Tokunaga: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.